In pharmacology, the synthetic form of cortisol is referred to as hydrocortisone, and is used as an antagonist in the treatment of allergies and inflammation as well as substitute supplementation in cortisol production deficiencies. When first introduced as a treatment for rheumatoid arthritis, it was referred to as Compound E.

Contents

Physiology

The amount of cortisol present in the serum undergoes diurnal variation, with the highest levels present in the early morning, and the lowest levels present around midnight, 3-5 hours after the onset of sleep. Information about the light/dark cycle is transmitted from the retina to the paired suprachiasmatic nuclei in the hypothalamus. The pattern is not present at birth (estimates of when it starts vary from two weeks to 9 months).[1]

Binding

Regulation

The primary control of cortisol is the pituitary gland peptide, adrenocorticotropic hormone (ACTH). ACTH probably controls cortisol by controlling movement of calcium into the cortisol secreting target cells.[2]. ACTH is in turn controlled by the hypothalamic peptide, corticotropin releasing factor (CRF), which is under nervous control. CRF acts synergisticly with arginine vasopressin, angiotensin II, and epinephrine[3]. When activated macrophages start to secrete interleukin-1 (IL-1), which synergistically with CRF increases ACTH, [4]T-cells also secrete glucosteroid response modifying factor (GRMF or GAF) as well as IL-1, both of which increase the amount of cortisol required to inhibit almost all the immune cells [5]. Thus immune cells take over their own regulation, but at a higher cortisol set point. Even so, the rise of cortisol in diarrheic calves is minimal over healthy calves and drops below with time. [6] The cells do not lose all of the fight or flight override because of interleukin-1's synergism with CRF. Cortisol even has a negative feedback effect on interleukin-1 [7] which must be especially useful against those diseases which gain an advantage by forcing the hypothalamus to secrete too much CRF, such as the endotoxin bacteria..The suppressor immune cells are not affected by GRMF, [8] so that the effective set point for the immune cells may be even higher than the set point for physiological processes. GRMF (called GAF in this reference) primarily affects the liver rather than the kidneys for some physiological processes [9].

A high potassium media, which stimulates aldosterone secretion in vitro, also stimulates cortisol secretion from the fasciculata zone of dog adrenals [10] unlike corticosterone, upon which potassium has no affect [11]. Potassium loading increases ACTH and cortisol in people also [12]. This is no doubt the reason why a potassium deficiency causes cortisol to decline (as just mentioned) and why a potassium deficiency causes a decrease in conversion of 11deoxycortisol to cortisol [13]. This probably contributes to the pain in rheumatoid arthritis since cell potassium is always low in that disease [14]

Factors affecting cortisol levels

Factors generally reducing cortisol levels

Omega 3 fatty acids, in a dose dependent manner (but not significantly),[18] can lower cortisol release influenced by mental stress[19] by suppressing the synthesis of interleukin-1 and 6 and enhance the synthesis of interleukin-2, where the former promote higher CRH release. Omega 6 fatty acids, on the other hand, acts inversely on interleukin synthesis.[citation needed]

Pharmacology

Hydrocortisone is the pharmaceutical term for cortisol used for oral administration, intravenous injection, or topical application. It is used as an immunosuppressive drug, given by injection in the treatment of severe allergic reactions such as anaphylaxis and angioedema, in place of prednisolone in patients who need steroid treatment but cannot take oral medication, and peri-operatively in patients on long-term steroid treatment to prevent an Addisonian crisis. It may be used topically for allergic rashes, eczema, psoriasis and certain other inflammatory skin conditions. It may also be injected into inflamed joints resulting from diseases such as gout.

Hydrocortisone creams and ointments are available without prescription in strengths ranging from 0.05% to 2.5%, depending on local regulations, with stronger forms available with prescriptions only.
Covering the skin after application increases the absorption and effect. Such enhancement is sometimes prescribed, but otherwise should be avoided to prevent over-dosing and systemic impacts.

Advertising for the dietary supplement CortiSlim originally (and falsely) claimed that it contributed to weight loss by blocking cortisol. The manufacturer was fined $1.2 million by the Federal Trade Commission in 2007 for false advertising, and no longer claims in their marketing that CortiSlim is a cortisol antagonist.[43]

Biochemistry

Biosynthesis

Cortisol is synthesized from cholesterol. The synthesis takes place in the zona fasciculata of the cortex of the adrenal glands. (The name cortisol comes from cortex.) While the adrenal cortex also produces aldosterone (in the zona glomerulosa) and some sex hormones (in the zona reticularis), cortisol is its main secretion. The medulla of the adrenal gland lies under the cortex and mainly secretes the catecholamines, adrenaline (epinephrine) and noradrenaline (norepinephrine) under sympathetic stimulation (more epinephrine is produced than norepinephrine, in a ratio 4:1).

Overall the net effect is that 11-beta HSD1 serves to increase the local concentrations of biologically active cortisol in a given tissue, while 11-beta HSD2 serves to decrease the local concentrations of biologically active cortisol.